TY - JOUR
T1 - Programmed degradation of a hierarchical nanoparticle with redox and light responsivity for self-activated photo-chemical enhanced chemodynamic therapy
AU - Wang, Shenqiang
AU - Yang, Letao
AU - Cho, Hyeon Yeol
AU - Dean Chueng, Sy Tsong
AU - Zhang, Hepeng
AU - Zhang, Qiuyu
AU - Lee, Ki Bum
N1 - Publisher Copyright:
© 2019 Elsevier Ltd
PY - 2019/12
Y1 - 2019/12
N2 - Chemodynamic therapy (CDT) has recently emerged as a promising treatment for cancer due to the high specificity of CDT towards tumor microenvironment (TME). However, the low efficiency of reactive oxygen species (ROS) generation and the robust ROS defensive mechanisms in cancer cells remain critical hurdles for current CDT. Addressing both challenges in a single platform, we developed a novel redox and light-responsive (RLR) nanoparticle with a core-shell structure. Remarkably, our hierarchical RLR nanoparticle is composed of an ultrasmall Fe3O4 nanoparticle engineered framework of hollow carbon matrix core and a nanoflower-like MnO2 shell. Under the abundant overexpressed glutathione (GSH) and acidic nature in TME, the RLR nanoparticle was programmed to degrade and self-activate CDT-induced cancer-killing by accelerating ROS generation via overcoming the ROS defensive mechanisms based on the depletion of intracellular GSH, the sequential production of theranostic ion species (e.g., Mn2+ and Fe2+), a spatiotemporal controllable photothermal hyperthermia and a redox triggered chemotherapeutic drug release. Additionally, the carbon framework of RLR nanoparticle could collapse by leaching of iron ions. An excellent selective and near-complete tumor suppression based on the RLR nanoparticles through a strong synergy between CDT, PTT and anti-cancer drugs was demonstrated via in vitro and in vivo anti-tumoral assays.
AB - Chemodynamic therapy (CDT) has recently emerged as a promising treatment for cancer due to the high specificity of CDT towards tumor microenvironment (TME). However, the low efficiency of reactive oxygen species (ROS) generation and the robust ROS defensive mechanisms in cancer cells remain critical hurdles for current CDT. Addressing both challenges in a single platform, we developed a novel redox and light-responsive (RLR) nanoparticle with a core-shell structure. Remarkably, our hierarchical RLR nanoparticle is composed of an ultrasmall Fe3O4 nanoparticle engineered framework of hollow carbon matrix core and a nanoflower-like MnO2 shell. Under the abundant overexpressed glutathione (GSH) and acidic nature in TME, the RLR nanoparticle was programmed to degrade and self-activate CDT-induced cancer-killing by accelerating ROS generation via overcoming the ROS defensive mechanisms based on the depletion of intracellular GSH, the sequential production of theranostic ion species (e.g., Mn2+ and Fe2+), a spatiotemporal controllable photothermal hyperthermia and a redox triggered chemotherapeutic drug release. Additionally, the carbon framework of RLR nanoparticle could collapse by leaching of iron ions. An excellent selective and near-complete tumor suppression based on the RLR nanoparticles through a strong synergy between CDT, PTT and anti-cancer drugs was demonstrated via in vitro and in vivo anti-tumoral assays.
KW - Drug delivery
KW - Hierarchical nanoparticle
KW - Photothermal therapy
KW - Programmed degradation
KW - Self-activated chemodynamic therapy
KW - Tumor microenvironment
UR - http://www.scopus.com/inward/record.url?scp=85072373831&partnerID=8YFLogxK
U2 - 10.1016/j.biomaterials.2019.119498
DO - 10.1016/j.biomaterials.2019.119498
M3 - 文章
C2 - 31557590
AN - SCOPUS:85072373831
SN - 0142-9612
VL - 224
JO - Biomaterials
JF - Biomaterials
M1 - 119498
ER -